Clinical Trial to Evaluate the Safety and Effectiveness of GDC-0032 When Given Alongside Tamoxifen

Phase 1

Completed

• Conditions: Breast Cancer
• Interventions: Drug: GDC-0032; Drug: Tamoxifen

• Registration Number: NCT02285179
• Lead Sponsor: The Netherlands Cancer Institute

Brief Summary

This study is designed as a phase 1 dose escalation study followed by a randomised phase II study. The study will be performed in three different centres: Addenbrooke \& Cambridge university (Cambridge, UK), Netherlands Cancer Institute Amsterdam), and Vall d'Hebron Hospital (Barcelona, Spain).

Three to six patients will be followed for one completed cycle of therapy (28 days) and subsequent enrolment of new cohorts will be based on the safety assessment in that first cycle and the documentation of dose limiting toxicities. To determine the safety and efficacy of tamoxifen in combination with the isoform selective Pi3K inhibitor GDC-0032 compared with tamoxifen alone.

Detailed Description

To determine the recommended phase II dose (RPTD) of GDC-0032 in combination with tamoxifen in hormone receptor positive, HER2 negative metastatic breast cancer patients who have progressed after prior endocrine treatment .Description of toxicity profile, severity and frequency of adverse events (observed with the combination of GDC-0032 and tamoxifen To evaluate the safety and tolerability of GDC-0032 in combination with tamoxifen, recording adverse events using CTCAE v. 4.0 criteria To describe the pharmacokinetics of GDC-0032 in combination with tamoxifen To investigate the possibility of major drug-drug interactions (PK) To obtain proof of target inhibition by selected pharmacodynamic measurements To look for preliminary evidence of anti-tumour activity To assess the status of potential biomarkers for drug response like PIK3CA gene mutations, relevant proteins and phospho-proteins in the PI3K pathway, circulating tumour DNA (ct-DNA) To assess germline DNA sequence for pharmacogenetics studies

Study Timeline

• Study First Submitted: 2014-10-21
• Study Start: 2014-11
• Study First Submitted QC: 2014-11-04
• Study First Posted: 2014-11-06
• Primary Completion: 2022-05-01
• Study Completion: 2022-05-01
• Status Verified: 2022-10
• Last Update Submitted: 2022-10-11
• Last Update Posted: 2022-10-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 189

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
tamoxifen and GDC-0032	GDC-0032	20 mg tamoxifen QD and 4 MG GDC-0032 QOD
tamoxifen and GDC-0032	Tamoxifen	20 mg tamoxifen QD and 4 MG GDC-0032 QOD
tamoxifen and placebo	Tamoxifen	20 mg tamoxifen QD and placebo QOD

Primary Outcome Measures

Name	Time	Method
Number of patients with MTD toxicity	4 weeks	MTD toxicity will be assessed in the first 28 days of treatment

Secondary Outcome Measures

Name	Time	Method
Safety Number of patients with adverse events	2 year	Number of patients with adverse events
Response Number of patients with a response to protocol treatment	2 year	Number of patients with a response to protocol treatment
Pharmacokinetics Number of patients with germline DNA sequence	12 months	Number of patients with germline DNA sequence

Trial Locations

Locations (14)

Reinier de Graaf Gasthuis; 🇳🇱 Delft, Netherlands

Haaglanden Medisch Centrum; 🇳🇱 Den Haag, Netherlands

Gustave Roussy; 🇫🇷 Paris, France

MUMC; 🇳🇱 Maastricht, Netherlands

University of Cambridge; 🇬🇧 Cambridge, United Kingdom

Antoni van Leeuwenhoek; 🇳🇱 Amsterdam, Netherlands

Hospital Clínic de Barcelona; 🇪🇸 Barcelona, Spain

Hospital Arnau de Vilanova; 🇪🇸 Lleida, Spain

Hospital Universitari Sant Joan de Reus; 🇪🇸 Tarragona, Spain

Hospital Germans Trias i Pujol; 🇪🇸 Badalona, Spain

Vall d'Hebron University Hospital/VHIO; 🇪🇸 Barcelona, Spain

Ziekenhuis Groep Twente; 🇳🇱 Hengelo, Netherlands

Hospital ICO-Hospitalet (Bellvitge); 🇪🇸 Barcelona, Spain

Deventer Ziekenhuis; 🇳🇱 Deventer, Netherlands